The tick-borne encephalitis virus (TBEV) complex is a group of viruses that cause severe neurotropic disease and up to 30% mortality. While these viruses can be found in many parts of the world, the largest impact of disease occurs in Europe and Russia, where approximately 14,000 hospitalized TBEV cases occur annually. Furthermore, the majority of TBEV cases are considered to be subclinical, indicating a higher incidence of TBEV infection than is generally recognized. The tick-borne encephalitis complex includes TBEV (e.g., European, Siberian, and Far Eastern subtypes), as well as Omsk hemorrhagic fever, Kyasanur forest disease, Langat, Louping ill, Negishi, and Powassan viruses.
TBEV is in the family Flaviviridae, genus Flavivirus and is composed of a positive-sense single stranded RNA genome that contains 5′ and 3′ non-coding regions (NCR) and a single open reading frame encoding 10 proteins. The proteins are co- and post-translationally cleaved by viral and host proteins to derive three structural proteins (capsid (C), membrane (M), and envelope (E)), and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). The non-structural proteins regulate viral transcription and replication and attenuate antiviral responses, while the structural proteins compose the outer shell of the virus and are, therefore, significant effectors of host immunogenicity.